Document Detail

Effects of an antistroke agent MCl-186 on cerebral arachidonate cascade.
MedLine Citation:
PMID:  7996477     Owner:  NLM     Status:  MEDLINE    
Activation of the cerebral arachidonate (AA) cascade is one of the major causes of edema and tissue injury in cerebral ischemia, particularly after reperfusion. The cascade produces toxic oxygen radicals responsible for peroxidative neurodegeneration and synthesizes, the potent edematous inducer, leukotrienes. The present study was undertaken to evaluate the effect of MCl-186 (3-methyl-1-phenyl-pyrazolin-5-one), a radical scavenger and antioxidant which has beneficial anti-ischemic actions, on the cerebral AA cascade. Postischemic treatment with MCl-186 (1.0 and 3.0 mg/kg i.v.) significantly inhibited the aggravation of cortical edema seen 60 min after recirculation following 30 min of ischemia in gerbils. An antilipoxygenase agent, FPL-55712 (7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2- hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid, monosodium salt; 10 mg/kg i.v.) or AA-861 ((2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinon e; 60 mg/kg i.p.) was also effective in this model; however, indomethacin (4 mg/kg i.p.), a cyclooxygenase inhibitor, was ineffective. Concomitant treatment with MCl-186 (0.1-3.0 mg/kg i.v.) remarkably inhibited the swelling observed 24 hr after cortical infusion of AA (80 micrograms) in rats. Similarly, antilipoxygenase agents clearly inhibited the AA-induced edema. Furthermore, postischemic treatment with MCl-186 (0.3-3.0 mg/kg i.v.) inhibited the facilitation of cerebral leukotriene synthesis seen 15 min after recirculation following 30 min of ischemia in gerbils. These findings suggest that the site of action of MCl-186 as an anti-ischemic agent may be closely associated with the cerebral AA cascade, especially the lipoxygenase system, activated by ischemia-reperfusion.
T Watanabe; M Egawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  271     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-01-17     Completed Date:  1995-01-17     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1624-9     Citation Subset:  IM    
Pharmaceutical Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
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MeSH Terms
Antipyrine / analogs & derivatives*,  pharmacology
Arachidonic Acid / metabolism*
Brain / drug effects*,  metabolism
Brain Edema / prevention & control
Cerebrovascular Disorders / prevention & control*
Chromones / pharmacology
Free Radical Scavengers*
Rats, Wistar
Superoxides / metabolism
Reg. No./Substance:
0/Chromones; 0/Free Radical Scavengers; 11062-77-4/Superoxides; 40786-08-1/FPL 55712; 506-32-1/Arachidonic Acid; 60-80-0/Antipyrine; 89-25-8/phenylmethylpyrazolone

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